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Study of MK-3475 (Pembrolizumab) in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma After Treatment With Platinum-based and Cetuximab Therapy (MK-3475-055/KEYNOTE-055)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02255097
Recruitment Status : Completed
First Posted : October 2, 2014
Results First Posted : July 6, 2017
Last Update Posted : June 28, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Tracking Information
First Submitted Date  ICMJE September 30, 2014
First Posted Date  ICMJE October 2, 2014
Results First Submitted Date  ICMJE April 20, 2017
Results First Posted Date  ICMJE July 6, 2017
Last Update Posted Date June 28, 2022
Actual Study Start Date  ICMJE October 24, 2014
Actual Primary Completion Date April 22, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2022)
  • Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Up to 36 months ]
    ORR was assessed by RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
  • Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 36 months ]
    Participants with a strong PD-L1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD-L1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
  • Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to 27 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
  • Number of Participants Discontinuing Study Drug Due to an AE [ Time Frame: Up to 24 months ]
    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
Original Primary Outcome Measures  ICMJE
 (submitted: September 30, 2014)
  • Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) [ Time Frame: Up to 3 years ]
  • Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to 27 months ]
  • Number of Participants Discontinuing Study Drug Due to an AE [ Time Frame: Up to 25 months ]
  • ORR by RECIST 1.1 in Programmed Cell Death Ligand 1 (PD-L1)-Positive Participants [ Time Frame: Up to 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2022)
  • Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a positive PD-L1 expression status were evaluated for ORR by RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
  • Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors [ Time Frame: Up to 76.9 months ]
    Participants with a HPV-positive tumor biopsy were evaluated for ORR by RECIST 1.1. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
  • Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Up to 76.9 months ]
    ORR was assessed by modified RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.
  • Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a tumor proportion score ≥1%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.
  • Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a strong positive PD-L1 expression status were evaluated for ORR by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a tumor proportion score ≥50%. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. If imaging shows disease progression (PD) imaging was repeated 4 weeks later to confirm progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions and new measurable lesions, taking as reference the smallest sum recorded since treatment started. Participants with missing data were considered non-responders.
  • Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Up to 76.9 months ]
    DOR was based on RECIST 1.1 and measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
  • Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a positive PD-L1 expression status were evaluated for DOR based on RECIST 1.1. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
  • Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a strong PD-L1 expression status were evaluated for DOR based n RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. DOR was measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR was censored at the last tumor assessment date if a responder did not have PD or death. Non-responders were not included in the analysis. The lower and upper limits were estimated at the time of data cutoff. DOR was analyzed by the Kaplan-Meier method for censored data and reported in months.
  • Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Up to 76.9 months ]
    PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
  • Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a positive PD-L1 expression status were evaluated for PFS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
  • Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a strong PD-L1 expression status were evaluated for PFS by modified RECIST 1.1. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. PFS was defined as the time from the first day of study treatment to the first documented PD per RECIST 1.1 or death due to any cause, whichever occurred first. Using RECIST 1.1, PD was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm the sum of lesions, OR the appearance of new lesions. PFS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
  • Overall Survival (OS) in All Participants [ Time Frame: Up to 76.9 months ]
    OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
  • Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a positive PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and PD-L1 positive was defined as a PD-L1 combined positive score ≥1%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
  • Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants [ Time Frame: Up to 76.9 months ]
    Participants with a strong PD-L1 expression status were evaluated for OS. PD-L1 expression was determined by IHC and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. OS was defined as the time from the first day of study treatment to death due to any cause. OS was analyzed by the Kaplan-Meier method for censored data and reported in months. Participant data were censored at last assessment.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2014)
  • ORR by Modified RECIST 1.1 in All Participants [ Time Frame: Up to 3 years ]
  • ORR by Modified RECIST 1.1 in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
  • ORR by Modified RECIST 1.1 in Human Papilloma Virus (HPV)-Positive Participants [ Time Frame: Up to 3 years ]
  • Progression-free Survival (PFS) in All Participants [ Time Frame: Up to 3 years ]
  • PFS in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
  • Overall Survival (OS) in All Participants [ Time Frame: Up to 3 years ]
  • OS in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
  • Response Duration in All Participants [ Time Frame: Up to 3 years ]
  • Response Duration in PD-L1-Positive Participants [ Time Frame: Up to 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of MK-3475 (Pembrolizumab) in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma After Treatment With Platinum-based and Cetuximab Therapy (MK-3475-055/KEYNOTE-055)
Official Title  ICMJE A Phase II Clinical Trial of Single Agent Pembrolizumab (MK-3475) in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Who Have Failed Platinum and Cetuximab
Brief Summary

This is a study of single-agent pembrolizumab (MK-3475) in participants with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed on platinum-based and cetuximab therapy. The primary study hypothesis is that pembrolizumab will provide a clinically meaningful objective response rate (ORR).

With protocol amendment 05 (02-Jan-2018), once study participants have achieved the study objective or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Squamous Cell Carcinoma
Intervention  ICMJE Biological: pembrolizumab
Other Names:
  • MK-3475
  • KEYTRUDA®
Study Arms  ICMJE Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 24 months
Intervention: Biological: pembrolizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 3, 2016)
172
Original Estimated Enrollment  ICMJE
 (submitted: September 30, 2014)
150
Actual Study Completion Date  ICMJE June 18, 2021
Actual Primary Completion Date April 22, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Histologically- or cytologically-confirmed recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
  • Tumor progression or recurrence within 6 months of the last dose of any number of platinum-based and cetuximab therapy lines in the adjuvant, primary, recurrent, or metastatic setting; must be resistant (not responding) to both platinum and cetuximab
  • Available tissue for biomarker analysis
  • Measurable disease based on RECIST 1.1 as determined by central review
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use 2 adequate methods of contraception starting with the screening visit through 120 days after the last dose of pembrolizumab
  • Male participants with a female partner(s) of childbearing potential must be willing to use 2 adequate methods of contraception from screening through 120 days after the last dose of pembrolizumab

Exclusion criteria:

  • Disease that is suitable for local therapy administered with curative intent
  • Currently receiving treatment in a study of an investigational agent or using an investigational device <= 4 weeks prior to the first dose of trial medication
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial medication
  • Not recovered from AEs due to a previously administered therapy
  • Known additional malignancy that is progressing or requires active treatment excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cancer
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Active, non-infectious pneumonitis
  • Active infection requiring systemic therapy
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial medication
  • Human immunodeficiency virus (HIV)
  • Hepatitis B or C
  • Received live vaccine within 30 days of planned start of study therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Denmark,   Norway,   United States
 
Administrative Information
NCT Number  ICMJE NCT02255097
Other Study ID Numbers  ICMJE 3475-055
2014-002447-18 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Current Responsible Party Merck Sharp & Dohme LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Merck Sharp & Dohme LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme LLC
PRS Account Merck Sharp & Dohme LLC
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP